Rodlet Cells

The rodlet cell is an enigmatic and little-understood cell type in teleost fishes. The rodlet cell has been
studied for more than a century, but its function and true nature remain unclear. Rodlet
cells are more than a mere scientific curiosity: whatever it may be, rodlet cells seem to
be involved in the response to disease and environmental insult. Since fishes are the most
ancient group of vertebrates, a thorough understanding of their physiology is important to
dealing with similar questions in higher vertebrate classes.

The rodlet cell is found only in bony fishes. The name comes from the appearance
of what is presumed to be the mature stage: an ovoid cell with a basally-located nucleus
and several conspicuous "rodlets" enclosed in a fibrous capsule. Though there are distinct
differences of morphology in the rodlet cells found in different species of fish, the general
pattern is the same in all of those species in which they been identified.

Rodlet cells have occasionally been reported from vertebrates other than fishes, but the reports are few and unreliable.
The consensus among rodlet cell researchers is that they occur only in teleosts and are not found in
amphibians, as was once thought to be the case. They may be present in cartilaginous fishes, but no indisputable
evidence for this is as yet available.

The rodlet cell was discovered by Thèlohan in 1892, and for many years it was regarded as a protozoan parasite.
It was in fact named Rhabdospora thelohani, reflecting this belief of its origin. In the past 20 years,
however, the "parasite theory of origin" has fallen out of favor, and most investigators now regard the
rodlet cell as being of endogenous origin. What the exact site or organ of origin may be, and exactly what
the rodlet cell is for are still matters of debate; there are still some investigators who argue that the parasite
concept has some validity, suggesting that the cell may be endogenous, but the rodlets are some form of inclusion
body produced in response to a submicroscopic or perhaps viral infection. For a schematic representation of a
"typical" rodlet cell, click here.

Among those who regard the rodlet cell as a normal component of teleosts, most argue that they
play a role in the inflammatory response to certain types of physiological insult. The exact
type of stimulus that elicits their formation (or recruitment from a pre-existing cell type)
is not known. Rodlet cells can be found in many different types of tissues, and are often
associated with sites at which the fish has been obviously wounded or parasitized; several
papers have described experimental and case studies in which large numbers of rodlet cells
were found in such places. On the other hand, they can sometimes be found in places where
there is no obvious morphologic pathology.

Rodlet cells have been found in tissues arising from any of the three embryonic germ layers
(endoderm, mesoderm, or ectoderm); in some species they are exclusively found in tissues arising
from only one, or two; whereas in other species they may found be in tissues arising from any
rudiment. They are most commonly associated with epithelia, though they can be found in the
intercellular spaces of connective tissue as well.

Though rodlet cells have been clearly demonstrated in well over 100 species of teleosts,
they have not been found in every species, and there are many fishes from which they have never
been reported. If they are in fact endogenous cells, this variability in occurrence might be
ascribed to a situation in which rodlet cells have arisen independently in some evolutionary
lines of teleosts, but not others. This explanation is somewhat suspect, however, since their
presence is not consistent even in individual specimens of species in which they are known to
occur. As there currently are no reliable methods to induce their presence, nor to generate
large numbers of them for isolation and study at the molecular level, identifying any precursor
cells and clarifying the chemical nature of the capsule and rodlets is not yet possible.

The exact nature and function of the internal rodlets is obscure. Recent data suggests
that they are a crystallized proteinaceous material which solubilizes upon release.
Some studies have indicated the presence of DNA in the rodlets, but others have contradicted this finding.
Most investigators have found them to be negative to stains for carbohydrates or nucleic acids.
Some ultrastructural investigations have indicated a crystalline structure, but in most
electron micrographs the rodlets appear to be amorphous, with a high-density "core"
and a "halo" of lower density around that.

In keeping with their unpredictable appearance in a given specimen, some other things about rodlet cells are variable. Though the general cell morphology is
the same in all cases, there are slight but perceptible differences of detail, as the image above shows. Rodlets vary from one species to another with respect
to their density, relative sizes of the core and halo, and length; there are some significant differences in shape as well. The capsule surrounding the cell
may or may not show internal densities that are similar to the anchor plaques of mammalian smooth muscle cells. Most investigators regard the capsule as contractile,
but if this is the case it has not been definitely proven that the typical contractile proteins actin and myosin are present in it. The "mature" cell, one
containing well-defined rodlets and presumably in a condition ready for their release is polarized. The nucleus is basally located, the rodlets
are distinctly oriented towards the point of release (which is always at the opposite end of the cell from the nucleus) and the structure of the capsule
is altered at the release point.

If the rodlet cell is near or in a blood vessel, it may exhibit behavior reminiscent of some mammalian leukocytes:
"margination" at the periphery of the vessel occurs, and attachment stalks are formed.

In the image to the left, rodlet cells in the circulation of an angelfish (Pterophyllum scalare scalare) are present
inside the lumen of a large blood vessel behind the eye. They are marginating and forming attachment stalks, in most cases.
Those that do will discharge their contents into the extracellular spaces around the blood vessel. A few rodlet cells are also
visible in the extravascular CT space; these may be ones attracted to the site by cytokines; or they may be on course to becoming the
cells in the vessel. It is not possible to determine solely from morphology which direction the cells are "migrating"
with respect to the vessel wall.

The images above show marginated rodlet cells in the vascular system of an angelfish; the electron micrograph
to the right was made from the same specimen as the light micrograph. The lower rodlet cell in the EM image has
developed the fibrillar "stalk" (Arrow) that is often associated with the anchorage of these cells on the inner surface
of the vessel .

The sequence of release of the rodlet cell's contents is well established. First the cell becomes oriented
towards the site at which the contents will be discharged, which is almost always at an epithelial surface.
A typical discharge site is into the lumen of a blood vessel, for example. Rodlet cells in the interstitial
spaces become associated with an overlying epithelium; sometimes an "attachment stalk" is formed, which contains
microfilaments or microtubules at this site, which appears to "anchor" the cell to the site. The next event
is the apparent dissolution of the capsule at the point of contact with the overlying epithelium and the release
of cellular contents. Intact rodlets can be released, and invariably mitochondria and/or vacuoles of some type
(perhaps derived from endoplasmic reticulum) are released as well. Discharge of the contents does not appear
to injure the adjacent epithelium.